Lithium diisopropylamide → Ethyl 2-(2-chloro-6-fluorophenyl)-3-(4-methylcyclohexyl)-3-oxopropionate

HRID 376251Notes

Reaction equation

HRID 376251 reaction equation
C([N-]C(C)C)(C)C.[Li+].[Cl:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[C:11]=1[CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19].[CH3:23][CH:24]1[CH2:29][CH2:28][CH:27]([C:30](Cl)=[O:31])[CH2:26][CH2:25]1>O1CCCC1>[Cl:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[C:11]=1[CH:17]([C:30]([CH:27]1[CH2:28][CH2:29][CH:24]([CH3:23])[CH2:25][CH2:26]1)=[O:31])[C:18]([O:20][CH2:21][CH3:22])=[O:19]

Participants

5

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 2733231Ethyl 2-chloro-6-fluorophenylacetateHCID 129863574-Methylcyclohexane-1-carbonyl chloride

Product 1

HCID 19361668Ethyl 2-(2-chloro-6-fluorophenyl)-3-(4-methylcyclohexyl)-3-oxopropionateYield 106.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

Lithium diisopropylamide (0.18 mol) in tetrahydrofuran (270 ml) is added to a mixture of ethyl (2-chloro-6-fluorophenyl)acetate (38.1 g, 0.175 mol) and THF (200 ml) at -70° C. The reaction mixture is stirred for 2 hours at about -70° C. 4-Methylcyclohexanecarboxylic acid chloride (28.25 g, 0.175 mol) is added and the reaction mixture is allowed to warm up to room temperature over night. The reaction mixture is then quenched with hydrochloric acid (5N, 60 ml) and most of the organic solvent is distilled off under reduced pressure. From the remainder the product is extracted with light petroleum (200 ml). The organic layer is separated, washed with water, dried with magnesium sulphate and concentrated in vacuo to yield a yellow oil (63.5 g). This is filtered through silica (light petroleum, 3% ethyl acetate) to yield a pale yellow oil (27.2 g). The product is used in the next step without further purification.

Workup

  1. temperatureto warm up to room temperature over night
  2. customThe reaction mixture is then quenched with hydrochloric acid (5N, 60 ml) and most of the organic solvent
  3. distillationis distilled off under reduced pressure
  4. extractionFrom the remainder the product is extracted with light petroleum (200 ml)
  5. customThe organic layer is separated
  6. washwashed with water
  7. dry with materialdried with magnesium sulphate
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-11271ffa8afd4c7da6c27ef32e409b42
Source dataset
uspto-grants-2000_02
Patent number
US06020338

Reaction notes

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